title: Novel 3,3-disubstituted pyrrolidines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors.
abstract: A series of 3,3-disubstituted pyrrolidine monoamine triple reuptake inhibitors were discovered. Analogues with low nanomolar potency, good human in vitro microsomal stability and in vitro permeability, and low drug-drug interaction potential are described. One example showed in vivo anti-depressant-like effects in the mouse tail suspension assay with a minimum effective dose of 30 mg/kg i.p.
authors.affiliation: Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Bannwart
authors.forename: David S
authors.initials: DS
authors.lastname: Carter
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Cai
authors.forename: Jason C
authors.initials: JC
authors.lastname: Choy
authors.forename: Robert
authors.initials: R
authors.lastname: Greenhouse
authors.forename: Saul
authors.initials: S
authors.lastname: Jaime-Figueroa
authors.forename: Pravin S
authors.initials: PS
authors.lastname: Iyer
authors.forename: Clara J
authors.initials: CJ
authors.lastname: Lin
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Lucas
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lynch
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Madera
authors.forename: Amy
authors.initials: A
authors.lastname: Moore
authors.forename: Kerem
authors.initials: K
authors.lastname: Ozboya
authors.forename: Lubica
authors.initials: L
authors.lastname: Raptova
authors.forename: Ralf
authors.initials: R
authors.lastname: Roetz
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Schoenfeld
authors.forename: Karin Ann
authors.initials: KA
authors.lastname: Stein
authors.forename: Sandra
authors.initials: S
authors.lastname: Steiner
authors.forename: Marzia
authors.initials: M
authors.lastname: Villa
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Weikert
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Zhai
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D013623:Tail / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D018765:Dopamine Uptake Inhibitors; D011759:Pyrrolidines; D012701:Serotonin; D009638:Norepinephrine